The Udall Center for Excellence in Parkinson Disease Research at the Mayo Clinic is an integrated, multi-disciplinary research program focusing on of the Genetics and Molecular Biology of Parkinsonism. The Udall Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section with its longitudinal studies of Parkinson disease (PD) and a focus on the clinical genetics of familial Parkinsonism, a large brain bank of Parkinsonian disorders and strong institutional commitment to PD research and education. All components of the Udall Center are based in Jacksonville, Florida, although core resources in Rochester, Minnesota, particularly the Division of Biomedical Statistics will be used. Mayo Foundation educational resources, including sponsored seminar series and graduate level educational courses on PD and other neurodegenerative disorders are also utilized. The proposal is highly innovative and original in that it addresses the intriguing interaction between two molecules with surprising similarities, tau and a-synuclein, both of which are strongly implicated as critical factors in pathogenesis of parkinsonian disorders. The clinical, genetic and pathologic studies proposed capitalize on inherent strengths of the Udall Center investigators and unique clinical, genetic and pathological resources that have been built over the years due to the fervent devotion of investigators to better understanding PD and related disorders. The Center also brings established investigators in complementary areas of research (Drs. Rademakers and Petrucelli) to the task of understanding how tau is related PD and how tau-directed therapies may translate into novel treatments for PD and parkinsonian tauopathies. The proposed Center will have three projects and four cores with an overarching theme to understand the role of tau in PD and parkinsonian tauopathies. Project 1, entitled Identification of novel parkinsonian genes by whole-genome sequencing, is led by Rosa Rademakers, PhD. Project 2, entitled Genetic determinants of a-synuclein and tau pathology in Parkinsonism, is led by Dennis W. Dickson, MD. Project 3, entitled Identification and testing of novel compounds to treat Parkinsonism, is led by Leonard Petrucelli, PhD. Core A (Administration) and Core D (Neuropathology) are led by Dennis W. Dickson, MD. Core B (Clinical) is led by Zbigniew K. Wszoiek, MD. Core C (Genetics) is led by Owen A. Ross, PhD.